Bortezomib in combination with intermediate‐dose dexamethasone and continuous low‐dose oral cyclophosphamide for relapsed multiple myeloma

• Published in: British journal of haematology Vol. 138; no. 3; pp. 330 - 337
• Main Authors: Kropff, Martin, Bisping, Guido, Schuck, Elke, Liebisch, Peter, Lang, Nicola, Hentrich, Markus, Dechow, Tobias, Kröger, Nicolaus, Salwender, Hans, Metzner, Bernd, Sezer, Orhan, Engelhardt, Monika, Wolf, Hans‐Heinrich, Einsele, Hermann, Volpert, Sarah, Heinecke, Achim, Berdel, Wolfgang E., Kienast, Joachim
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2007; Blackwell
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Boronic Acids - administration & dosage; Bortezomib; chemotherapy; Chi-Square Distribution; cyclophosphamide; Cyclophosphamide - administration & dosage; Dexamethasone - administration & dosage; Disease-Free Survival; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; myeloma; Pyrazines - administration & dosage; Recurrence; relapsed; Survival Rate; Antineoplastic agent; Relapse; Myeloma; Multiple dose; Immunoglobulinopathy; Lymphoproliferative syndrome; Corticosteroid; Immunopathology; Drug combination; Bortezomib; Dexamethasone; Hematology; Steroid hormone; Low dose; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Alkylating agent; Oxazaphosphinane derivatives; Chemotherapy; Cyclophosphamide; Treatment; Analog; Nitrogen mustard; Dipeptides; relapsed
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2007.06656.x

Summary A phase 2 trial was performed to study the combination of bortezomib (VELCADE®) with intermediate‐dose dexamethasone (DEX), and continuous low‐dose oral cyclophosphamide (CY) in patients with relapsed multiple myeloma (MM). Fifty‐four patients with advanced MM were enroled to receive eight 3‐week treatment cycles with bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11, followed by three 5‐week cycles with bortezomib 1·3 mg/m2 on days 1, 8, 15, and 22. Within all cycles, DEX 20 mg/d was given orally on the day of bortezomib injection and the day thereafter. In addition, patients received CY continuous oral treatment at a dose of 50 mg/d p.o. once daily. Fifty patients completing at least one treatment cycle were evaluable for response. Complete, partial, and minor responses occurred in 16%, 66% and 8% of patients, respectively; overall response rate 90% (efficacy analysis). Median event‐free survival was 12 months, with a median overall survival of 22 months. Adverse events (AE) of grades 3 or 4 occurring in at least 10% of patients comprised leucopenia, infection, herpes zoster, thrombocytopenia, neuropathy and fatigue. Bortezomib combined with DEX and CY is a highly effective treatment for relapsed MM at an acceptable rate of grade 3/4 AE. Antiviral prophylaxis appears to be mandatory.